The genus Klebsiella belongs to the family Enterobacteriaceae and is divided into at least 4 species. They are gram-negative, capsulated, oxidase-negative, non-motile, straight rods. They are facultative anaerobes, having both respiratory and fermentative metabolisms. Most strains can use citrate and glucose as their sole carbon source. Some strains can fix nitrogen. They are commonly found in intestines, clinical samples, soil, water and grains.
Klebsiella pneumoniae, a Gram-negative enteric bacterium, is a common pathogen that causes hospital-acquired urinary tract infections, septicemia and pneumonia as well as community-acquired pneumonia. Community-acquired pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae complicated with metastatic meningitis and endophthalmitis has emerged globally, especially in Asia. The mortality rates are 10% for those with Klebsiella pneumoniae PLA, and 30-40% among those with metastatic meningitis. Persons who survived meningitis usually have severe neurological sequelae. Patients who suffer from K. pneumoniae endophthalmitis usually become blind in the affected eye. Therefore, prevention, rapid diagnosis and proper treatment for this invasive disease are required.
There are more than 75 traditional capsular serotypes defined by antisera in Klebsiella. Immunological diagnosis is usually used to identify the capsular serotypes of Klebsiella. However, the anti-sera are expensive and have to be purchased from limited resources. Dietlinde Rieger-Hug and Stephan Stirm conducted a comparative study if host capsule depolymerase associated with Klebsiella bacteriophages and proves that the viral depolymerases are very specific (Dietlinde Rieger-Hug and Stephan Stirm, Comparative study of host capsule depolymerases assoaciated with Klebsielle bacteriophages, 1981, Virology, 113, 363-378). A study of capsular serotypes in bacteremic Klebsiella pneumoniae isolates in Taiwan showed that 52 out of 94 isolates (55%) from community-acquired infections and 48 out of 64 isolates (75%) from noaocomial infections were non-typable (Tsay R W, Siu L K, Fung C P, Chang F Y. Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection. Arch Intern Med. 2002 May 13; 162(9):1021-7). A previous survey from Australia on the serotypes of 293 K. pneumoniae isolates reported that 88 isolates (30%) were non-typable by counter-current immunoelectrophoresis (CIE), while 54 had a positive reaction to more than one serotype (Jenney A W, Clements A, Farn J L, Wijburg O L, McGlinchey A, Spelman D W, Pitt T L, Kaufmann M E, Liolios L, Moloney M B, Wesselingh S L, Strugnell R A. Seroepidemiology of Klebsiella pneumoniae in an Australian Tertiary Hospital and its implications for vaccine development. J Clin Microbiol. 2006; 44(1):102-7). Therefore, it is difficult to identify Klebsiella pneumoniae using serotyping.
Capsular serotype K1 and K2 are considered to be the predominant virulent strains of Klebsiella pneumoniae. Further investigation has found K1 to be the most common serotype isolated from patients with Klebsiella pneumoniae PLA and endophthalmitis (Fung C P, Chang F Y Lee S C, et al. Gut 2002; 50:420-4). K1 has been further investigated as the most common serotype isolated from patients with Klebsiella pneumoniae liver abscess and endophthalmitis. Mucoviscosity has been documented as a virulence factor of Klebsiella pneumoniae. Using transposon mutagenesis, a virulence gene, magA, was identified, which was involved in the hypermucoviscosity phenotype and also played an important role in resistance to serum and phagocytosis. It is reported in “The Journal of Infectious Diseases, 2006; 193:645-54” that magA and its flanking regions might be associated with capsular polysaccharide biosynthesis, and magA-containing chromosomal region encodes capsular structure and is specific for the K1 serotype.
Bacteriophages are bacterial viruses that attach to their specific hosts and kill them by internal replication and bacterial lysis involving a complex lytic cycle involving several structural and regulatory genes. Bacteriophages are very specific in that they only attack their targeted bacterial hosts. Accordingly, bacteriophages are considered to be a potentially powerful cure for and diagnosis means of bacterial infections. Previous studies report that bacteriophage-infected encapsulated bacteria often carried the capsule-degrading enzymes, so such enzymes may be used as a marker to identify bacterial species and detect and treat bacterial infection. U.S. Pat. No. 7,405,066 discloses a bacteriophage capable of lysing a Propionibacterium acnes bacterium and its use in the treatment of acne.
However, a number of bacteriophages specific to Klebsiella pneumoniae strains have not been found. There remains in the art a need for the discovery of novel bacteriophages specific to Klebsiella pneumoniae capsular type, and identifying methods for using these bacteriophages in several critical areas, including therapy and diagnosis of infection caused by Klebsiella pneumoniae. 